Clearing the haze: investigating the clinical pharmacology of cannabinoids

Abstract

Clearing the Haze: Investigating the Clinical Pharmacology of Cannabinoids examines the pharmacology, therapeutic potential, and safety of cannabinoids through a series of controlled clinical studies in healthy volunteers. The thesis focuses on the two principal cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and addresses several assumptions that currently shape medical and public perspectives on cannabis-based therapies.

The work demonstrates that CBD does not attenuate the psychotropic effects of oral THC, but can instead enhance them by increasing plasma concentrations of THC and its active metabolite through inhibition of cytochrome P450-mediated metabolism. In addition, CBD was shown to increase plasma concentrations of amitriptyline, highlighting clinically relevant drug–drug interaction risks at commonly used doses. Neurophysiological studies found no evidence for direct effects of CBD on cortical excitability, questioning the extent of its intrinsic anti-epileptic properties. Finally, the thesis evaluates selonabant, a CB1 receptor antagonist, as a targeted pharmacological treatment for acute cannabinoid intoxication.

Together, these studies contribute to a more evidence-based and mechanistic understanding of cannabinoid pharmacology and support a precision-pharmacology approach to cannabinoid therapeutics.